The work outlined in this proposal includes the building of an instrument capable of measuring the Circular Intensity Differential Scattering (CIDS) of chiral molecules; that is, the difference in scattered cross-sections for the two incident circular polarizations exhibited by optically active molecules. This effect originally described as an artifact in the circular dichroism spectra of certain molecular systems has been recently characterized theoretically by us. We have also succeeded in performing the first experimental measurements of this effect as a function of the scattering angle. This newly developed technique has proven extremely useful in characterizing the structural details of macromolecular aggregates in solution. We have built an earlier version of this instrument at the University of California, Berkeley. The instrument proposed here is an improved version of the original design and will allow nearly a 50-fold increase in sensitivity. The highest source in the apparatus will be provided by an Argon-ion laser and the CIDS measurements made at a fixed wavelength of the incident light as a function of the scattering angle. This instrument will be used to study of folding of chromatin both in vitro and in situ. While the basic structure of chromatin has been established, little is known on the way this nucleoprotein complex achieves its higher order organization. There is increasing evidence, however, that the mechanisms of genetic control in the cell are directly connected to the changes that a chromatin undergoes along the cell cycle. We propose here to study the differential scattering of chromatin in situ as a function of the cell cycle, to obtain information about the factors that control and stabilize the condensed forms of chromatin in the cell nucleus. Parallel experiments of the effect of solution parameters in the structure of extracted chromatin are also described. These studies will allow us to monitor continuously the conformational changes induced in chromatin by external agents such as ionic strength, temperature, polyions, etc. Underlying these studies is the possibility of ultimately being able to characterize and interpret CIDS and CD contributions of biomolecular and subcellular structures.